1887

Abstract

Antimicrobial peptides (APs) are important host weapons against infections. Nearly all APs are cationic and their microbicidal action is initiated through interactions with the anionic bacterial surface. It is known that pathogens have developed countermeasures to resist these agents by reducing the negative charge of membranes, by active efflux and by proteolytic degradation. Here we uncover a new strategy of resistance based on the neutralization of the bactericidal activity of APs by anionic bacterial capsule polysaccharide (CPS). Purified CPSs from K2, serotype 3 and increased the resistance to polymyxin B of an unencapsulated mutant. Furthermore, these CPSs increased the MICs of polymyxin B and human neutrophil -defensin 1 (HNP-1) for unencapsulated , and PAO1. Polymyxin B or HNP-1 released CPS from capsulated , serotype 3 and overexpressing CPS. Moreover, this material also reduced the bactericidal activity of APs. We postulate that APs may trigger the release of CPS, which in turn will protect bacteria against APs. We found that anionic CPSs, but not cationic or uncharged ones, blocked the bactericidal activity of APs by binding them, thereby reducing the amount of peptides reaching the bacterial surface. Supporting this, polycations inhibited such interaction and the bactericidal activity was restored. We postulate that trapping of APs by anionic CPSs is an additional selective virulence trait of these molecules, which could be considered as bacterial decoys for APs.

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2008-12-01
2019-10-24
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